Dairy and nondairy beverage consumption for childhood atopic eczema: what health advice to give?

BACKGROUND: Many parents of children with atopic eczema (AE) practise empirical dietary avoidance and supplementation, and seek healthcare advice on whether consumption of dairy and nondairy beverages may be beneficial or detrimental for this condition. AIM: We investigated if frequency of consumption of beverages was associated with disease severity and quality of life (QoL). METHODS: Parent-reported frequency of drinks and beverages were recorded in consecutive children with AE, and disease severity (Nottingham Eczema Severity Score; NESS), QoL (Children's Dermatology Life Quality Index; CDLQI), skin hydration (SH), transepidermal water loss (TEWL), blood pressure (BP), resting heart rate (RHR) and body mass index (BMI) were evaluated. RESULTS: AE was associated with worse QoL than miscellaneous non-AE skin diseases (P < 0.001). Compared with children without AE, there was a trend for children with AE to drink less milk (P = 0.06) and more miscellaneous beverages (such as Chinese herbal tea and soymilk; P = 0.03). In children with AE, NESS correlated with CDLQI (ρ = 0.66, P < 0.001) and reduced SH (ρ = -0.32, P < 0.001), whereas CDLQI correlated with a higher RHR (ρ = 0.25, P < 0.01). Multiple logistic regression showed that male sex (OR = 0.44, 95% CI 0.20-0.97; P = 0.04) and drinking fresh milk (OR = 0.42, 95% CI 0.20-0.93; P = 0.03) were independent factors associated with less severe disease. Moderate to severe impairment of CDLQI was associated with NESS (OR = 1.48, 95% CI 1.28-1.71; P < 0.001) and RHR (OR = 1.05, 95% CI 1.02-1.08; P < 0.01) but not with reported habits of beverage consumption. Concerning cardiovascular health in AE, frequency of formula milk consumption was associated with RHR (ρ = 0.17, P = 0.04), and soft drink consumption was associated with higher systolic blood pressure (SBP) (ρ = 0.18, P = 0.04). CONCLUSION: This study provides evidence for parental/patient guidance. Children with AE who reported more fresh milk consumption had less severe disease. There was no correlation between consumption of nondairy beverages with disease severity or QoL, but frequency of soft drink consumption correlated with SBP. With these results being supported by a literature review, it is reasonable to advise parents that fresh milk can be consumed by unsensitized children with AE. Soft drinks and other beverages should not be consumed in excess for optimal cardiovascular health and for other health reasons.

Zinc-finger protein 331, a novel putative tumor suppressor, suppresses growth and invasiveness of gastric cancer.

Zinc-finger protein 331 (ZNF331), a Kruppel-associated box zinc-finger protein gene, was identified as a putative tumor suppressor in our previous study. However, the role of ZNF331 in tumorigenesis remains elusive. We aimed to clarify its epigenetic regulation and biological functions in gastric cancer. ZNF331 was silenced or downregulated in 71% (12/17) gastric cancer cell lines. A significant downregulation was also detected in paired gastric tumors compared with adjacent non-cancer tissues. In contrast, ZNF331 was readily expressed in various normal adult tissues. The downregulation of ZNF331 was closely linked to the promoter hypermethylation as evidenced by methylation-specific PCR, bisulfite genomic sequencing and reexpression by demethylation agent treatment. DNA sequencing showed no genetic mutation/deletion of ZNF331 in gastric cancer cell lines. Ectopic expression of ZNF331 in the silenced cancer cell lines MKN28 and HCT116 significantly reduced colony formation and cell viability, induced cell cycle arrests and repressed cell migration and invasive ability. Concordantly, knockdown of ZNF331 increased cell viability and colony formation ability of gastric cancer cell line MKN45. Two-dimensional gel electrophoresis and mass spectrometry-based comparative proteomic approach were applied to analyze the molecular basis of the biological functions of ZNF331. In all, 10 downstream targets of ZNF331 were identified to be associated with regulation of cell growth and metastasis. The tumor-suppressive effect of ZNF331 is mediated at least by downregulation of genes involved in cell growth promotion (DSTN, EIF5A, GARS, DDX5, STAM, UQCRFS1 and SET) and migration/invasion (DSTN and ACTR3), and upregulation of genome-stability gene (SSBP1) and cellular senescence gene (PNPT1). A novel target of ZNF331 (DSTN) was functionally validated. Overexpression of DSTN in BGC-823 cells increased colony formation and migration ability. In conclusion, our results suggest that ZNF331 possesses important functions for the suppression of gastric carcinogenesis as a novel functional tumor-suppressor gene.

A novel interplay between oncogenic PFTK1 protein kinase and tumor suppressor TAGLN2 in the control of liver cancer cell motility.

The PFTK1 gene encodes a cdc2-related serine/threonine protein kinase that has been shown to confer cell migratory properties in hepatocellular carcinoma (HCC). However, the prognostic value and biological mechanism by which PFTK1 promotes HCC motility remain largely unknown. Here, we showed from tissue microarray that common upregulations of PFTK1 in primary HCC tumors (n=133/180) correlated significantly with early age onset (40 years), advance tumor grading and presence of microvascular invasion (P0.05). To understand downstream phosphorylated substrate(s) of PFTK1, phospho-proteins in PFTK1 expressing and knockdown Hep3B cells were profiled by two-dimensional-polyacrylamide gel electrophoresis mass spectrometric analysis. Protein identification of differential spots revealed ß-actin (ACTB) and transgelin2 (TAGLN2) as the two most profound phosphorylated changes affected by PFTK1. We verified the presence of TAGLN2 serine phosphorylation and ACTB tyrosine phosphorylation. Moreover, reduced TAGLN2 and ACTB phosphorylations in PFTK1-suppressed Hep3B corresponded to distinct actin depolymerizations and marked inhibition on cell invasion and motility. Given that TAGLN2 is a tumor suppressor whose function has been ascribed in cancer metastasis, we examined if TAGLN2 is an intermediate substrate in the biological path of PFTK1. We showed in PFTK1-suppressed cells that knockdown of TAGLN2 over-rode the inhibitory effect on cell invasion and motility, and a recovery on actin polymerization was evident. Interestingly, we also found that unphosphorylated TAGLN2 in PFTK1-suppressed cells elicited strong actin-binding ability, a mechanism that possibly halts the actin cytoskeleton dynamics. Site-directed mutagenesis of TAGLN2 suggested that PFTK1 regulates the actin-binding affinity of TAGLN2 through the S83 and S163 residues, which if mutated can significantly affect HCC cell motility. Taken together, our data propose a novel, oncogene-tumor suppressor interplay, where oncogenic PFTK1 confers HCC cell motility through inactivating the actin-binding motile suppressing function of TAGLN2 via phosphorylation.

Differential expression of microRNAs in plasma of patients with colorectal cancer: a potential marker for colorectal cancer screening.

OBJECTIVE: MicroRNAs (miRNAs) have been shown to offer great potential in the diagnosis of cancer. We investigated whether plasma miRNAs could discriminate between patients with and without colorectal cancer (CRC). METHODS: This study was divided into three phases: (1) marker discovery using real-time PCR-based miRNA profiling on plasma, corresponding cancerous and adjacent non-cancerous colonic tissues of five patients with CRC, along with plasma from five healthy individuals as controls; (2) marker selection and validation by real-time quantitative RT-PCR on a small set of plasma; and (3) independent validation on a large set of plasma from 90 patients with CRC, 20 patients with gastric cancer, 20 patients with inflammatory bowel disease (IBD) and 50 healthy controls. RESULTS: Of the panel of 95 miRNAs analysed, five were upregulated both in plasma and tissue samples. All the five miRNAs were validated on the plasma of 25 patients with CRC and 20 healthy controls. Both miR-17-3p and miR-92 were significantly elevated in the patients with CRC (p<0.0005). The plasma levels of these markers were significantly reduced after surgery in 10 patients with CRC (p<0.05). Further validation with an independent set of plasma samples (n = 180) indicated that miR-92 differentiates CRC from gastric cancer, IBD and normal subjects. This marker yielded a receiver operating characteristic curve area of 88.5%. At a cut-off of 240 (relative expression in comparison to RNU6B snRNA), the sensitivity was 89% and the specificity was 70% in discriminating CRC from control subjects. CONCLUSION: MiR-92 is significantly elevated in plasma of patients with CRC and can be a potential non-invasive molecular marker for CRC screening.